Investigation of ICAM-1 and β3 Integrin Gene Variations in Patients with Brain Tumors

  • Yilmaz, Umit (Department of Molecular Medicine, The Institute of Experimental Medicine, Istanbul University) ;
  • Zeybek, Umit (Department of Molecular Medicine, The Institute of Experimental Medicine, Istanbul University) ;
  • Kahraman, Ozlem Timirci (Department of Molecular Medicine, The Institute of Experimental Medicine, Istanbul University) ;
  • Kafadar, Ali Metin (Department of Neurosurgery, Cerrahpasa Faculty of Medicine, Istanbul University) ;
  • Toptas, Bahar (Department of Molecular Medicine, The Institute of Experimental Medicine, Istanbul University) ;
  • Yamak, Nesibe (Department of Molecular Medicine, The Institute of Experimental Medicine, Istanbul University) ;
  • Celik, Faruk (Department of Molecular Medicine, The Institute of Experimental Medicine, Istanbul University) ;
  • Yaylim, Ilhan (Department of Molecular Medicine, The Institute of Experimental Medicine, Istanbul University)
  • Published : 2013.10.30


Background: Primary brain tumors constitute a small percent of all malignant cancers, but their etiology remains poorly understood. ${\beta}3$ integrin (ITGB3) has been recognized to play influential roles in angiogenesis, tumor growth and metastasis. Intercellular adhesion molecule-1 (ICAM-1) is a surface glycoprotein important for tumor invasion and angiogenesis. The aim of this study was to investigate whether specific genetic polymorphisms of ICAM-1 and ITGB3 could be associated with brain cancer development and progression in a Turkish population. Our study is the first to our knowledge to investigate the relationship between brain tumor risk and ICAM-1 and ${\beta}3$ integrin gene polymorphisms. Materials and Methods: The study covered 92 patients with primary brain tumors and 92 age-matched healthy control subjects. Evaluation of ${\beta}3$ integrin (Leu33Pro (rs5918)) and ICAM-1 (R241G (rs1799969) and K469E (rs5498)) gene polymorphisms was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: According to results of our research, the A allele of the ICAM-1 R241G gene polymorphism appeared to be a risk factor for primary brain tumors (p<0.001). Similarly, the frequency of the A mutant allele of ICAM-1 R241G was statistically significant in patients with brain tumors classified as glioma (p<0.001). When allele and genotype distributions of ICAM-1 K469E, ICAM-1 R241G and ${\beta}3$ integrin Leu33Pro gene polymorphisms were evaluated with age, sex, and smoking, there were no statistically significant differences. Haplotype analysis revealed that the frequencies of GAC (rs1799969-rs5498-rs5918) and GAT (rs1799969-rs5498-rs5918) haplotypes were significantly lower in patients as compared with controls (p=0.001; p=0.036 respectively). Conclusions: This study provides the first evidence that ICAM-1 R241G SNP significantly contributes to the risk of primary brain tumors in a Turkish population. In addition, our results suggest that ICAM-1 R241G in combination ICAM-1 K469E may have protective effects against the development of brain cancer.


Cancer;brain tumor;polymorphism;ICAM-1;${\beta}3$-integrin


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